How to taper nitroglycerin (glyceryl trinitrate) infusion?

From the Guidelines

Nitroglycerin infusion should be tapered gradually to avoid rebound hypertension or angina, typically by decreasing the infusion rate by 5-10 mcg/min every 5-10 minutes until reaching the lowest effective dose, as recommended by the ACC/AHA 2007 guidelines 1.

Tapering Process

The tapering process should be individualized based on the patient's response and the duration of therapy.

• For patients who have been on higher doses (>100 mcg/min) or prolonged therapy (>24-48 hours), a more conservative approach should be used by reducing the rate by 5-10 mcg/min every 15-30 minutes.
• Throughout the tapering process, the patient's blood pressure, heart rate, and symptoms of angina or chest discomfort should be closely monitored.
• If the patient develops recurrent symptoms or significant blood pressure elevation during tapering, the previous effective dose should be reinstated and the tapering rate slowed.

Alternative Medications

Alternative anti-anginal or antihypertensive medications should be optimized before discontinuing nitroglycerin completely.

Rationale

The gradual tapering is necessary because prolonged nitroglycerin exposure can lead to nitrate tolerance and compensatory vasoconstriction, which may result in rebound symptoms if the medication is stopped abruptly, as noted in the guidelines 1.

Key Considerations

• The patient's clinical status and response to tapering should guide the tapering process.
• The use of non-tolerance-producing nitrate regimens, such as lower doses and intermittent dosing, can help minimize the risk of rebound symptoms.
• The ACC/AHA 2007 guidelines provide a framework for the management of patients with unstable angina/non-ST-elevation myocardial infarction, including the use of nitrates and the tapering of nitroglycerin infusion 1.

From the FDA Drug Label

DOSAGE & ADMINISTRATION ... Although the usual starting adult dose range reported in clinical studies was 25 mcg/min or more, these studies used PVC administration sets. THE USE OF NON-ABSORBING TUBING WILL RESULT IN THE NEED FOR REDUCED DOSES. ... When using a non-absorbing infusion set, the initial dosage should be 5 mcg/min delivered through an infusion pump capable of exact and constant delivery of the drug. Subsequent titration must be adjusted to the clinical situation, with dose increments becoming more cautious as partial response is seen Initial titration should be in 5 mcg/min increments, with increases every 3-5 minutes until some response is noted. If no response is seen at 20 mcg/min, increments of 10 and later 20 mcg/min can be used. Once a partial blood pressure response is observed, the dose increase should be reduced and the interval between increases should be lengthened

The FDA drug label does not answer the question.

From the Research

Tapering Nitroglycerin Infusion

To taper nitroglycerin infusion, several factors should be considered, including the development of tolerance and the patient's response to dose escalation.

• Tolerance to nitroglycerin infusion can be overridden by dose escalation in the majority of patients for a significant period of time 2.
• The development of tolerance can be prevented by providing a daily low-nitrate interval, with a 12-h patch-free interval recommended to prevent tolerance in most patients 3.
• Dose escalation can be repeated in patients who develop tolerance, with complete restoration of nitroglycerin action possible over 24 hours in half the patients and over 48 hours in one third of the patients 2.
• The effects of intravenous nitroglycerin on hemodynamics and myocardial metabolism have been studied, with results showing that nitroglycerin can have beneficial effects on cardiac performance and metabolism 4.

Mechanisms of Tolerance

• Tolerance to organic nitrates occurs when the agents are administered in an attempt to provide therapeutic effects throughout 24 hours each day 5.
• The mechanisms responsible for nitrate tolerance are not fully understood, but it is thought that intermittent therapy with a daily low-nitrate interval can prevent tolerance development 3, 5.
• Different nitrate preparations may have varying effects on the development of tolerance, with some studies suggesting that certain preparations may be more likely to cause tolerance than others 6.

Clinical Implications

• The development of tolerance to nitroglycerin infusion can have significant clinical implications, including reduced efficacy and increased risk of adverse effects 2, 5.
• Clinicians should be aware of the potential for tolerance to develop and take steps to prevent it, such as providing a daily low-nitrate interval and monitoring patient response to dose escalation 3, 2.
• Further research is needed to fully understand the mechanisms of tolerance and to develop effective strategies for preventing and managing it 5, 6.